Reverse engineering of force integration during mitosis in the Drosophila embryo

The mitotic spindle is a complex macromolecular machine that coordinates accurate chromosome segregation. The spindle accomplishes its function using forces generated by microtubules (MTs) and multiple molecular motors, but how these forces are integrated remains unclear, since the temporal activation profiles and the mechanical characteristics of the relevant motors are largely unknown. Here, we developed a computational search algorithm that uses experimental measurements to ‘reverse engineer' molecular mechanical machines. Our algorithm uses measurements of length time series for wild-type and experimentally perturbed spindles to identify mechanistic models for coordination of the mitotic force generators in Drosophila embryo spindles. The search eliminated thousands of possible models and identified six distinct strategies for MT–motor integration that agree with available data. Many features of these six predicted strategies are conserved, including a persistent kinesin-5-driven sliding filament mechanism combined with the anaphase B-specific inhibition of a kinesin-13 MT depolymerase on spindle poles. Such conserved features allow predictions of force–velocity characteristics and activation–deactivation profiles of key mitotic motors. Identified differences among the six predicted strategies regarding the mechanisms of prometaphase and anaphase spindle elongation suggest future experiments

Roles of motor proteins in building microtubule-based structures: a basic principle of cellular design

AbstractEukaryotic cells must build a complex infrastructure of microtubules (MTs) and associated proteins to carry out a variety of functions. A growing body of evidence indicates that a major function of MT-associated motor proteins is to assemble and maintain this infrastructure. In this context, we examine the mechanisms utilized by motors to construct the arrays of MTs and associated proteins contained within the mitotic spindle, neuronal processes, and ciliary axonemes. We focus on the capacity of motors to drive the ‘sliding filament mechanism’ that is involved in the construction and maintenance of spindles, axons and dendrites, and on a type of particle transport called ‘intraflagellar transport’ which contributes to the assembly and maintenance of axonemes

Mitosis, microtubules, and the matrix

The mechanical events of mitosis depend on the action of microtubules and mitotic motors, but whether these spindle components act alone or in concert with a spindle matrix is an important question

Spawning and early development of captive yellowfin tuna (Thunnus albacares)

In this study we describe the courtship and spawning behaviors of captive yellowfin tuna (Thunnus albacares), their spawning periodicity, the influence of physical and biological factors on spawning and hatching, and egg and early-larval development of this species at the Achotines Laboratory, Republic of Panama, during October 1996 through March 2000. Spawning occurred almost daily over extended periods and at water temperatures from 23.3° to 29.7°C. Water temperature appeared to be the main exogenous factor controlling the occurrence and timing of spawning. Courtship and spawning behaviors were ritualized and consistent among three groups of broodstock over 3.5 years. For any date, the time of day of spawning (range: 1330 to 2130 h) was predictable from mean daily water temperature, and 95% of hatching occurred the next day between 1500 and 1900 h. We estimated that females at first spawning averaged 1.6−2.0 years of age. Over short time periods (<1 month), spawning females increased their egg production from 30% to 234% in response to shortterm increases in daily food ration of 9% to 33%. Egg diameter, notochord length (NL) at hatching, NL at first feeding, and dry weights of these stages were estimated. Water temperature was significantly, inversely related to egg size, egg-stage duration, larval size at hatching, and yolksac larval duration

Glucose effects on long-term memory performance : duration and domain specificity.

Rational; Previous research has suggested that long term- verbal declarative memory is particularly sensitive to enhancement by glucose loading, however investigation of glucose effects on certain memory domains has hitherto been neglected. Therefore domain specificity of glucose effects merits further elucidation. Objectives; The aim of the present research was to provide a more comprehensive investigation of the possible effects of glucose administration on different aspects of memory by i) contrasting the effect of glucose administration on different memory domains (implicit/ explicit memory; verbal/ non-verbal memory, recognition/ familiarity processes), ii) investigating whether potential effects on memory domains differ depending on the dose of glucose administered (25g versus 60g), iii) exploring the duration of the glucose facilitation effect (assessment of memory performance 35 min and 1 week after encoding). Methods; a double blind, between- subjects design was used to test the effects of administration of 25 and 60g glucose on memory performance. Results; Implicit memory was improved following administration of 60g of glucose. Glucose supplementation failed to improve face recognition performance but significantly improved performance of word recall and recognition following administration of 60g of glucose. However, effects were not maintained one-week following encoding. Conclusions; Improved implicit memory performance following glucose administration has not been reported before. Furthermore the current data tentatively suggest that level of processing may determine the required glucose dosage to demonstrate memory improvement and that higher dosages may be able to exert effects on memory pertaining to both hippocampal and non-hippocampal brain regions

Estimating the burden of COVID-19 on mortality, life expectancy and lifespan inequality in England and Wales : a population-level study

Objective: To determine the impact of the COVID-19 pandemic on mortality, life expectancy and lifespan inequality in the first half of 2020 (from week 1 to week 26 starting June 22) in England and Wales. Design: Demographic analysis of all-cause mortality from week 1 through week 26 of 2020 using publicly available death registration data from the Office for National Statistics. Setting and population: England and Wales population by age and sex in 2020. Main outcome measure: Age and sex-specific excess mortality risk and deaths above a baseline adjusted for seasonality in the first half of 2020. We additionally provide estimates of life expectancy at birth and lifespan inequality defined as the standard deviation in age at death. Results: We estimate that there have been 53,937 (95% Prediction Interval: 53,092, 54,746) excess deaths in the first half of 2020, 54% of which occurred in men. Excess deaths increased sharply with age and men experienced elevated risks of death in all age groups. Life expectancy at birth dropped 1.7 and 1.9 years for females and males relative to the 2019 levels, respectively. Lifespan inequality also fell over the same period. Conclusions: Quantifying excess deaths and their impact on life expectancy at birth provides a more comprehensive picture of the full COVID-19 burden on mortality. Whether mortality will return to - or even fall below - the baseline level remains to be seen as the pandemic continues to unfold and diverse interventions are put in place

Glucose enhancement of human memory: A comprehensive research review of the glucose memory facilitation effect

The brain relies upon glucose as its primary fuel. In recent years, a rich literature has developed from both human and animal studies indicating that increases in circulating blood glucose can facilitate cognitive functioning. This phenomenon has been termed the ‘glucose memory facilitation effect’. The purpose of this review is to discuss a number of salient studies which have investigated the influence of glucose ingestion on neurocognitive performance in individuals with (a) compromised neurocognitive capacity, as well as (b) normally functioning individuals (with a focus on research conducted with human participants). The proposed neurocognitive mechanisms purported to underlie the modulatory effect of glucose on neurocognitive performance will also be considered. Many theories have focussed upon the hippocampus, given that this brain region is heavily implicated in learning and memory. Further, it will be suggested that glucose is a possible mechanism underlying the phenomenon that enhanced memory performance is typically observed for emotionally laden stimuli

Shape coexistence at the proton drip-line: First identification of excited states in 180Pb

Excited states in the extremely neutron-deficient nucleus, 180Pb, have been identified for the first time using the JUROGAM II array in conjunction with the RITU recoil separator at the Accelerator Laboratory of the University of Jyvaskyla. This study lies at the limit of what is presently achievable with in-beam spectroscopy, with an estimated cross-section of only 10 nb for the 92Mo(90Zr,2n)180Pb reaction. A continuation of the trend observed in 182Pb and 184Pb is seen, where the prolate minimum continues to rise beyond the N=104 mid-shell with respect to the spherical ground state. Beyond mean-field calculations are in reasonable correspondence with the trends deduced from experiment.Comment: 5 pages, 4 figures, submitted to Phys.Rev.

Functional modulation of IFT kinesins extends the sensory repertoire of ciliated neurons in Caenorhabditis elegans

The diversity of sensory cilia on Caenorhabditis elegans neurons allows the animal to detect a variety of sensory stimuli. Sensory cilia are assembled by intraflagellar transport (IFT) kinesins, which transport ciliary precursors, bound to IFT particles, along the ciliary axoneme for incorporation into ciliary structures. Using fluorescence microscopy of living animals and serial section electron microscopy of high pressure–frozen, freeze-substituted IFT motor mutants, we found that two IFT kinesins, homodimeric OSM-3 kinesin and heterotrimeric kinesin II, function in a partially redundant manner to build full-length amphid channel cilia but are completely redundant for building full-length amphid wing (AWC) cilia. This difference reflects cilia-specific differences in OSM-3 activity, which serves to extend distal singlets in channel cilia but not in AWC cilia, which lack such singlets. Moreover, AWC-specific chemotaxis assays reveal novel sensory functions for kinesin II in these wing cilia. We propose that kinesin II is a “canonical” IFT motor, whereas OSM-3 is an “accessory” IFT motor, and that subtle changes in the deployment or actions of these IFT kinesins can contribute to differences in cilia morphology, cilia function, and sensory perception